Published 4:00 am, Friday, July 16, 2004

2004-07-16 04:00:00 PDT Bangkok -- With the quest for an AIDS vaccine coming up short, researchers in the desperate effort to find a way to slow the global pandemic are mining an array of low-tech solutions that hold surprising promise.

At the 15th International AIDS Conference, now drawing to a close, these simpler technologies are being explored with an increasing sense of urgency. Unfortunately, most of these technologies require extensive testing, the results of which may not be known for three to five years.

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A wide range of alternatives are currently being looked at:

-- Studies in Zimbabwe may determine whether women can gain a margin of protection by wearing a diaphragm to guard the cervix against HIV, the virus that causes AIDS.

-- A large-scale test in South Africa of a gel made from seaweed is one of several potential microbicides -- creams or jellies that kill viruses -- that could shield a woman from HIV even if her infected partner refuses to use a condom.

-- Major trials expected to be completed by 2007 in Uganda, Kenya and South Africa may settle once and for all whether male circumcision reduces the risk of HIV. A number of earlier surveys in Africa and India have suggested that lack of male circumcision -- the removal of the foreskin -- more than doubles the risk of contracting the AIDS virus.

-- Among the most exciting and promising low-tech prevention methods is the prospect of cutting the risk of HIV in half by treating genital herpes for pennies a day. Tests under way in Africa -- and set to begin shortly in San Francisco -- would try to improve the odds against HIV by taming herpes infections with the cheap antiviral drug acyclovir. Men and women with herpes simplex 2, the common genital herpes virus, may run two to five times the risk of contracting HIV.

Herpes lesions in the skin or mucous tissue create tiny avenues for the AIDS virus to slip into the bloodstream. In some sub-Saharan African nations, genital herpes rates among women run as high as 70 percent.

A presentation in Bangkok by researcher Dr. Christina Lindan of UCSF found an HIV infection rate of 25 percent among 2,000 men who also tested positive for genital herpes at sexually transmitted disease clinics in Bombay. That compares with a 6 percent rate among those who did not have herpes -- strong evidence that herpes dangerously increases vulnerability to AIDS.

Two studies under the direction of Dr. Connie Celum, an infectious disease specialist at the University of Washington, may determine whether two pills a day of acyclovir, a generic antiviral drug costing about 6 cents a tablet, can cut HIV infection risks by at least 50 percent.

"The question is: Can you disrupt the synergy between HIV and herpes?" Celum explained.

One test -- a large, multicountry study that will be conducted in part in San Francisco -- will provide acyclovir to women who have herpes but are HIV-negative and then test them for the AIDS virus every three months. In 2006, the study will reveal whether the women whose herpes is under control have a lower rate of HIV infection.

A second acyclovir study, set to begin in Africa and India, will test whether giving acyclovir to people infected with both HIV and herpes reduces the chance that they will infect their HIV-negative partners.

Meanwhile, researchers are looking for prevention methods that can help women tip the scales against HIV. High on the list: female condoms. Larger and more expensive than traditional condoms that shield the penis, female condoms fit into the vagina and provide a similar barrier against HIV infection.

"It's the only thing we've got in a epidemic that's been rapidly feminized," said Dr. Helen Rees, of Chris Hani Barangwanath Hospital in Johannesburg. Rees notes that 77 percent of HIV infections in South Africa are among women. "We've got something here, and we are not using it," she said.

Studies have shown that men in Africa do accept the female condom, and Rees described anecdotal reports from prostitutes saying that "when a man is drunk enough, he doesn't know about it anyway."

Another option, the female diaphragm, dates back to the mid-1800s, Zimbabwe researcher Dr. Michael Chrenje told reporters. In 2006, results may be available from a study -- designed by researchers at the UCSF AIDS Research Institute -- in which 4,500 HIV-negative women were recruited to use either a diaphragm and a moisturizing gel, or condoms and gel, before sexual intercourse.

Although the women will be counseled to have their sexual partner use a condom, in practice the partners are not likely to do so. If the diaphragm- wearing women have a lower HIV infection rate at the end of the study, it will provide strong evidence that this existing technology might be used to boost the odds against the virus for women who have few means of protection.

The holy grail of AIDS prevention technology for women would be an effective microbicide.

"Women are in desperate need of having something under their control as far as HIV prevention," said Zeda Rosenberg, chief executive of the International Partnership for for Microbicides, of Silver Spring, Md., which is calling for a $1 billion research effort.

Although six products are about to enter large-scale trials, Rosenberg predicted that a useful microbicide is still five to seven years away. One of the leading candidates is Carraguard, a microbicide under development by the Population Council, based in New York. The gel, which is derived from seaweed, is a protein that is already used as a food additive. It may kill the AIDS virus by altering the acid balance inside the vagina, and it is an attractive candidate because of its low cost. The large-scale test under way in South Africa will not yield results until 2006.

Another microbicide being tested is a topical form of the AIDS drug tenofovir, which is currently used orally in combination with other drugs to fight HIV. The pill form is manufactured by Gilead Sciences of Foster City.

"The idea of prevention is to get out in front of this epidemic," said Dr. Helene Gayle, director of AIDS programs for the Bill & Melinda Gates Foundation. "The bottom line is that these tools could save millions of lives over the next few years."